Broadcast History Gaps When Archival Material Exists: Inserting Peg Lynch and Ethel and Albert into Sitcom History

Lucy and Desi. Burns and Allen. Ozzie and Harriet. Ethel and Albert? The first three television couples tend to be the familiar husband-wife pairs that typify American 1950s sitcoms. These characters and their namesake programs, along with the Andersons in Father Knows Best and the Cleavers in Leave it to Beaver, are credited as templates for the domestic sitcom genre, where the narrative logic oscillates between morality lessons and outlandish plots to escape domestic life. When we study or reminisce about 1950s television, Ethel and Albert and their namesake program do not readily come to mind. However, the popularity of Ethel and Albert(1953-1956) on radio and television, and its critical acclaim, warrants examination as to why and how this program, and really any program with similar levels of notoriety in its time, remains obscure

Mutation of the co-chaperone Tsc1 in bladder cancer diminishes Hsp90 acetylation and reduces drug sensitivity and selectivity

The molecular chaperone Heat shock protein 90 (Hsp90) is essential for the folding, stability, and activity of several drivers of oncogenesis. Hsp90 inhibitors are currently under clinical evaluation for cancer treatment, however their efficacy is limited by lack of biomarkers to optimize patient selection. We have recently identified the tumor suppressor tuberous sclerosis complex 1 (Tsc1) as a new co-chaperone of Hsp90 that affects Hsp90 binding to its inhibitors. Highly variable mutations of TSC1 have been previously identified in bladder cancer and correlate with sensitivity to the Hsp90 inhibitors. Here we showed loss of TSC1 leads to hypoacetylation of Hsp90-K407/K419 and subsequent decreased binding to the Hsp90 inhibitor ganetespib. Pharmacologic inhibition of histone deacetylases (HDACs) restores acetylation of Hsp90 and sensitizes Tsc1-mutant bladder cancer cells to ganetespib, resulting in apoptosis. Our findings suggest that TSC1 status may predict response to Hsp90 inhibitors in patients with bladder cancer, and co-targeting HDACs can sensitize tumors with Tsc1 mutations to Hsp90 inhibitors

The clinical utility of testicular cancer risk loci

Three recent genome-wide association studies of testicular germ cell tumors have uncovered predisposition alleles in or near several genes, including KITLG, BAK1, SPRY4, TERT, ATF7IP, and DMRT1. The calculated per-allele odds ratio for variants in the region of KITLG is the highest reported for any malignancy so far. These findings are in agreement with epidemiological data indicating that testicular cancer has a higher heritability than most other cancers. Here, we discuss the question of whether the newly identified risk polymorphisms can be used to guide patient care

Новые возможности органосохраняющего лечения локализованного почечно-клеточного рака и его рецидива

Последнее десятилетие было ознаменовано более глубоким пониманием молекулярных путей, ответственных за развитие почечно-клеточного рака (ПКР), достижениями в системном лечении диссеминированного ПКР, а также многочисленными дискуссиями по поводу выбора наиболее оптимального варианта лечения локализованных форм опухоли. Учитывая многочисленные данные о развитии почечной недостаточности после хирургического лечения, а также возрастающее количество пациентов с ранними стадиями ПКР, важность органосохраняющего лечения нельзя недооценивать. Несмотря на отсутствие рандомизированных исследований, сравнивающих эффективность органосохраняющего лечения и радикальной нефрэктомии при ПКР, многочисленные ретроспективные данные указывают на сопоставимую эффективность обоих лечебных подходов при лучших показателях функции почек в случае органосохраняющего лечения. Поэтому органосохраняющее лечение все чаще используется как для открытых, так и для малоинвазивных хирургических вмешательств. В данном обзоре будут представлены данные, подтверждающие необходимость органосохраняющего лечения при ПКР, и описаны новые возможности метода, включая лапароскопические методики с участием роботизированной техники, аблацию и повторные хирургические вмешательства на почке.

Familial Renal Cancer: Molecular Genetics and Surgical Management

Familial renal cancer (FRC) is a heterogeneous disorder comprised of a variety of subtypes. Each subtype is known to have unique histologic features, genetic alterations, and response to therapy. Through the study of families affected by hereditary forms of kidney cancer, insights into the genetic basis of this disease have been identified. This has resulted in the elucidation of a number of kidney cancer gene pathways. Study of these pathways has led to the development of novel targeted molecular treatments for patients affected by systemic disease. As a result, the treatments for families affected by von Hippel-Lindau (VHL), hereditary papillary renal carcinoma (HPRC), hereditary leiomyomatosis renal cell carcinoma (HLRCC), and Birt-Hogg-Dubé (BHD) are rapidly changing. We review the genetics and contemporary surgical management of familial forms of kidney cancer

Understanding the Impact of Belzutifan on Treatment Strategies for Patients with VHL

Belzutifan was recently approved for the management of Von Hippel–Lindau disease (VHL). Given the morbidity of recurrent treatment, systemic therapy to reduce or eliminate the need for surgery has been long-awaited. Herein, we sought to gain insight about future utilization by surveying VHL  experts in the United States. A survey developed by members of the VHL Alliance (VHLA) Clinical Advisory Council was distributed to kidney cancer providers at VHLA and National Comprehensive Cancer Network (NCCN) centers. Surveys were administered on a secure web-based platform. A total of 60 respondents from 29 institutions participated. Urologists (50%) and medical oncologists (43%) represented the majority of participants. The majority (98%) of respondents anticipated that belzutifan’s approval would signifi-cantly change the current treatment landscape. Most reported that therapy should be continuous (76%). There was a difference in willingness to prescribe belzutifan by specialty (38% of urologists vs 91% of medical oncologists (P = 0.02). In individuals with renal tumors <3 cm, 36% would still recommend surveillance, while 36% would initiate belzutifan to prevent growth. In those with multifocal renal lesions and growth of a solitary tumor on belzutifan, 50% would proceed with only treatment of that site. In conclusion, VHL kidney cancer specialists anticipate a paradigm shift with the approval of belzutifan. Provider roles may change with movement away from surgical management. Opinions on treatment indications, such as when to initiate therapy and how to best salvage, vary widely and collaborative efforts among experts may assist in the development of clinical guidelines